Trends Endocrinol Metab. 2026 Mar 17:S1043-2760(26)00010-X. doi: 10.1016/j.tem.2026.01.010. Online ahead of print.
ABSTRACT
Familial partial lipodystrophy 2 (FPLD2) is a rare disease characterized by selective adipose tissue loss, expansion, and dysfunction, caused by pathogenic variants in LMNA encoding nuclear lamins A and C. Here, we synthesize current evidence on how nuclear shape abnormalities, impaired mechanosensing, blocked adipogenesis, chromatin remodeling, and altered lamin-binding partner interactions may contribute to FPLD2 pathology. Emerging data highlight chromatin and transcriptional dysregulation of lipogenic, mitochondrial, and inflammatory genes as central drivers, with other mechanisms acting in complementary ways. We also discuss depot-specific transcriptional remodeling that may explain differential adipose loss and expansion in FPLD2. Understanding how these mechanistic pathways converge across FPLD2 and other laminopathies may reveal new therapeutic targets to preserve adipose function.
PMID:41851000 | DOI:10.1016/j.tem.2026.01.010